Sexual dysfunction in both males and females has received a significant amount of popular attention with the greater concerns directed to the particular male problems of erectile capacity and penetration ability. Male sexual dysfunction associated with impotence is generally defined as the inability to attain or sustain an erection satisfactory for normal coitus. Prevalence of erectile problems, including premature ejaculation, has been estimated to be surprisingly high, perhaps as much as 45% worldwide. This is a particular concern among the over-50 male population in the United States, where estimates of impotency range from 18 to 75% for this age group.
Medical intervention for treatment of erectile dysfunction is becoming increasingly common. Surgical procedures, penile implants and pharmacological agents have been developed for treatment of male erectile dysfunction in recent years.
Surgical interventions employing penile implants and various patient-controlled mechanical devices are not uniformly successful nor are they appropriate in most situations. A serious disadvantage of treating erectile dysfunction with a surgical implant is the necessity to irreversibly damage the erectile tissues of the penis.
Pharmacological methods have been developed to treat male erectile dysfunction. The mechanism of erection is dependent on adequate blood flow to the spongy cavernous tissue of the penis, in paired spaces known as the corpora cavernosa. Control of blood flow to the corpora cavernosa involves the process of vasodilation of the cavernosal arteries.
It is now recognized that vasodilators acting on the penile arteries can be beneficial to achieving an erection. Orally administered vasodilators are currently the most widely accepted treatments for male erectile dysfunction. Such vasodilators include sildenafil. This compound is taken orally about one hour prior to intercourse because instant erection is not achieved with this drug. Unfortunately, this delay may lead to overdosing by patients seeking a more rapid response. While effective, this product may cause undesirable side effects such as headache, flushing, dyspepsia and in some cases abnormal vision such as increased sensitivity to light. Of greater concern, this drug may exacerbate pre-existing heart conditions. Furthermore, sildenafil must be taken on an empty stomach and must not be taken with alcohol.
A more rapid response in producing an erection has been found for sildenafil applied intranasally. The response is often within five minutes, and the drug is asserted to have fewer side effects than when administered orally. While reducing side effects, the drug nevertheless enters the circulatory system and is able to exert vasodilatory effects in areas other than the penis. Following the nasal route of administration, undesirable side effects can still be produced, some of which may be of medical concern.
Recognition of the problems associated with systemic administration of vasodilators has led to development of methods for local delivery of vasodilators to the tissues of the penis. For example, a semi-solid vehicle containing a vasodilator for insertion into the urethra has been formulated and shown to be effective in stimulating erection. Disadvantages of this method are the requirement for administration into the urethra, contributing to transient burning or tingling effects reported in some cases, and raising the possibility of urethral infection and scarring. This product is ineffective in up to 60% of patients.
An alternative and more direct route for delivery of vasodilators is injection into the corpus cavernosum of the penis. This “intracavernosal” route has been successfully used to deliver one or more vasodilators to achieve erections, and has led to the development of a treatment regimen known as intracavernosal pharmacotherapy (ICP).
Studies have led to the discovery of several vasodilators capable of provoking an erection. The use of papaverine for male erectile dysfunction has been reported. Papaverine is a vascular intracellular smooth muscle relaxant acting by its inhibitory effect on cyclic mononucleotide phosphodiesterases. However papaverine as monotherapy had an unpredictable response, and the drug must be administered in large volumes. Additionally, significant side effects associated with papaverine include the potential for prolonged erection and fibrosis of the corpus cavernosum.
Another vasodilator that has been used to achieve erection is phentolamine. Phentolamine alone does not reliably produce an erection sufficient for intercourse.
Prostaglandin E1 (PGE1) is a yet another vasodilator that effects an erection through its action as an alpha-adrenergic blocker. PGE1 has been formulated into suppositories for insertion into the urethra of men suffering from erectile dysfunction. As described above, this method of administration is disadvantageous due to risk of urethral infection and fibrosis. PGE1 has a short half life compared with papaverine and phentolamine. Intracavernosal injection of PGE1 can cause an erection of dose-dependent duration but, in a trial of this method, was associated with significant pain in a large percentage (up to 40%) of the subjects.
Several combinations of vasodilators have been used for treatment of impotence by the intracavernosal route. Success has been reported in a clinical study using a combination of papaverine and phentolamine in patients having vascular causes of impotence mostly associated with diabetes or atherosclerosis. Clinical success has also been reported in men with erectile dysfunction of neurogenic origin using a combination of papaverine, phentolamine and PGE1. The three-drug mixture has been regarded as more effective than PGE1 alone in inducing an erectile response, with a decreased incidence of pain. This drug combination also decreases the latency between injection and erection and allows a reduction in the total papaverine dose, reducing the risk of prolonged erection and potential incidence of fibrosis.
The collective experience of urologists reviewing clinical trials and treating patients with erectile dysfunction has led to an appreciation that despite impressive successes with some patients, no one therapy or composition can be applied across-the-board to treat all erectile problems.